Microbiota-derived acetate enhances host antiviral response via NLRP3.
Microbiota-derived acetate enhances host antiviral response via NLRP3.
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微生物群衍生的醋酸盐通过 NLRP3 增强宿主抗病毒反应
DOI：
10.1038/s41467-023-36323-4
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发表时间：
2023-02-06
影响因子：
16.6
通讯作者：
Meng, Guangxun
中科院分区：
文献类型：
--
作者：
Niu, Junling;Cui, Mengmeng;Yang, Xin;Li, Juan;Yao, Yuhui;Guo, Qiuhong;Lu, Ailing;Qi, Xiaopeng;Zhou, Dongming;Zhang, Chenhong;Zhao, Liping;Meng, Guangxun
病原性病毒感染是对人类健康的重大挑战。宿主对呼吸道病毒的免疫反应与肠道-肺轴的微生物群和代谢密切相关。已知宿主对甲型流感病毒(IAV)的防御涉及NLRP3炎症体的激活，然而，NLRP3保护功能背后的机制尚不完全清楚。在这里，我们显示了一种分离的细菌菌株，伪龙双歧杆菌NjM1，富含在Nlrp3−/−小鼠的肠道微生物区系中，可以保护野生型但不能保护Nlrp3缺陷小鼠免受新城疫病毒的感染。这一作用依赖于NjM1衍生的醋酸酯介导的I型干扰素(IFN-I)的促进产生。外源醋酸酯的应用再现了NjM1的保护作用。在机制上，NLRP3连接GPR43和MAV，促进MAV的寡聚化和信号转导；而醋酸酯促进MAV在GPR43参与时的聚集，导致干扰素-I的产生增加。因此，我们的数据支持NLRP3通过产醋酸菌介导干扰素-I诱导增强的模型，并表明乙酸乙酯-GPR43-NLRP3-MAVS-干扰素-I信号轴是治疗呼吸道病毒感染的潜在靶点。NLRP3炎症体在清除病毒呼吸道感染中起着关键作用，但其分子机制尚不完全清楚。在这里，作者表明，由肠道细菌产生的醋酸盐可能会在小鼠感染流感后促进NLRP3介导的I型干扰素的产生。
Pathogenic viral infections represent a major challenge to human health. Host immune responses to respiratory viruses are closely associated with microbiome and metabolism via the gut-lung axis. It has been known that host defense against influenza A virus (IAV) involves activation of the NLRP3 inflammasome, however, mechanisms behind the protective function of NLRP3 are not fully known. Here we show that an isolated bacterial strain, Bifidobacterium pseudolongum NjM1, enriched in the gut microbiota of Nlrp3−/− mice, protects wild-type but not Nlrp3 deficient mice against IAV infection. This effect depends on the enhanced production of type I interferon (IFN-I) mediated by NjM1-derived acetate. Application of exogenous acetate reproduces the protective effect of NjM1. Mechanistically, NLRP3 bridges GPR43 and MAVS, and promotes the oligomerization and signalling of MAVS; while acetate enhances MAVS aggregation upon GPR43 engagement, leading to elevated IFN-I production. Thus, our data support a model of NLRP3 mediating enhanced induction of IFN-I via acetate-producing bacterium and suggest that the acetate-GPR43-NLRP3-MAVS-IFN-I signalling axis is a potential therapeutic target against respiratory viral infections. The NLRP3 inflammasome plays a pivotal role in clearing viral respiratory infection, but the molecular mechanism is not fully known. Here authors show that acetate, produced by gut bacteria, may enhance NLRP3-mediated type I interferon production following influenza infection in mice.
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Toll样受体（TLR）3对病毒诱导的急性肺炎的有害贡献。
影响因子：
6.7
作者：
Le Goffic, Ronan;Balloy, Viviane;Lagranderie, Micheline;Alexopoulou, Lena;Escriou, Nicolas;Flavell, Richard;Chignard, Michel;Si-Tahar, Mustapha
通讯作者：
Si-Tahar, Mustapha
DOI：
10.1084/jem.20140825
发表时间：
2015-05-04
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Goritzka M;Makris S;Kausar F;Durant LR;Pereira C;Kumagai Y;Culley FJ;Mack M;Akira S;Johansson C
通讯作者：
Johansson C
DOI：
10.1038/nri3665
发表时间：
2014-05
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
5.4
作者：
Creager, Hannah M.;Kumar, Amrita;Belser, Jessica A.
通讯作者：
Belser, Jessica A.
影响因子：
64.8
作者：
Fukuda, Shinji;Toh, Hidehiro;Ohno, Hiroshi
通讯作者：
Ohno, Hiroshi